ACC Activation to Reward Predicts Response to Psychotherapy for MDD

Reward processing is impaired in a number of ways in major depressive disorder (MDD), including reduced neural responsiveness, activation and pleasure associated with rewarding stimuli. Anhedonia–the lack of enjoyment and interest in previously pleasurable activities–may be the most common symptom among individuals with MDD. It is associated with a range of negative outcomes, such as inferior treatment response, and neuroimaging studies have linked it with reduced mesocorticolimbic reward circuit responsiveness.

In addition, patients with MDD have been shown to have altered functioning and connectivity of the anterior cingulate cortex (ACC), which is involved in discerning external stimuli and monitoring reward feedback. Some findings indicate a connection between increased ACC activation and improved response to various treatment approaches for MDD. “Responses to rewards may be promising endophenotypes to understand not only the pathophysiology of MDD, but also biomarkers of response to antidepressant treatments,” according to the current paper. 

To that end, researchers at Duke University Medical Center and the University of North Carolina at Chapel Hill School of Medicine examined whether neural reward responses assessed before treatment would predict participants’ responses to a psychotherapy approach called Behavioral Activation Treatment for Depression (BATD). The intervention aims to decrease avoidant behaviors while increasing exposure to rewarding activities.

Patients who met DSM-IV criteria for MDD underwent functional magnetic resonance imaging (fMRI) before participating in approximately 12 weekly sessions of BATD. Participants were excluded from the MDD group if they had co-occurring psychiatric disorders, active suicidal ideation, and several other characteristics. The final sample consisted of 33 patients with MDD and 20 controls.

After a practice session for observation and adjustment of participants’ reaction times, they completed the monetary incentive delay task (MID) twice during fMRI to allow for assessment of changes in neural activation from one round to the next in response to BATD. Depression severity was assessed with the Beck Depression Inventory-II (BDI) at baseline, and then every 2 weeks throughout treatment and again at the last session.

Though the treatment response was variable, BDI scores decreased by an average of 10.54 points after BATD. Congruent with previous findings, in the MDD group vs controls, there was a reduction in sustained activation of the right nucleus accumbens (NAcc) in response to rewards. Additionally, sustained ACC activation during rewarding events predicted better treatment response to BATD. Baseline anhedonia severity and reaction times were predictors of treatment response.

Considering that many patients do not respond to conventional antidepressant treatments, the “identification of methods to match specific patients with the most appropriate, personalized treatment option is an important way to help relieve the societal burden of MDD,” the authors concluded. It could be, for example, that BATD is a particularly effective approach for patients whose reward processing is relatively intact.

Reference

Carl H, Walsh E,  Eisenlohr-Moul T, et al. Sustained anterior cingulate cortex activation during reward processing predicts response to psychotherapy in major depressive disorder. J Affect Disord. 2016; 203:204-12.